Chronic viral hepatitis, in particular Hepatitis C (HCV) infection, has emerged as an important cause of morbidity and mortality in individuals infected with the human immunodeficiency virus (HIV). The effect of alcohol, which has been identified as an important determinant of the natural history of HCV infection, is less well-established in HCV/HIV co-infection. The hypothesis proposes that in HIV/HCV co-infected individuals, host genetic factors are important in progression of liver disease and in the development of fibrosis and that these genetic factors may explain variations in the effects of HIV and alcohol on liver disease severity. Allelic variations in proteins critical to the inflammatory response may alter the hepatic response to both alcohol and HCV in the setting of HIV co-infection as well as the severity and progression of chronic disease. Our preliminary data suggest host genetic factors play a critical role in progression of HIV/HCV disease. This application aims to evaluate HCV mono-infected and HIV/HCV co-infected subjects, utilizing known cohorts of both HCV and HIV/HCV patients, with available clinical and virologic data. It will determine the prevalence of selected polymorphisms in HLA Class C; Natural Killer cell immunoglobulin-like receptors; cytokines and cytokine receptors. The established research infrastructure for longitudinal follow-up of subjects in CFAR-supported studies and the availability of stored biologic specimens, including DNA, will serve as a platform for cutting-edge laboratory science and collaborative studies, and is a unique resource for addressing these study aims: 1) To define the allelic variation in cytokines and their receptors (CCR5, CCR5 promoter, ICAM-1, IgE Fc receptor, IL-1 alpha, IL4-Receptor, 1L-10, P selectin and VCAM) and to define the Killer cell Immunoglobulin-like receptors (KIR) genotype and human leukocyte antigen (HLA) Class C expression in HIV and HCV co-infected and HCV mono-infected individuals and 2) To correlate the allelic variations noted above to the clinical, virologic factors and histologic stage of HCV disease to determine the effect of alcohol and HIV on severity and progression of HCV infection. [unreadable] [unreadable]